A Better Way To Evaluate The Effect Of Drugs And Toxic Substances On Cells

February 11, 20194 min read

A new method called MicroColonyChip can precisely evaluate chemical effects on cell survival much faster than existing gold-standard techniques.

It allows scientists to observe ultra-fine changes in cell survival.

All diseases are disruptions at the cellular level. To treat them, it’s important to know its cause. To know the cause of a disease, it’s important to understand how individual cells change under certain conditions.

Analyzing the effects of toxic compounds on different kinds of cells is necessary for creating drugs. Each drug is designed to destroy specific target cells. In recent decades, scientists have greatly enhanced their potential for identifying molecular anomalies responsible for several diseases, including some genetically complex diseases.

This has been made possible by analyzing the survival rates of cells. Today, we have several state-of-the-art techniques that measure cells survival with unprecedented accuracy. However, most of them involve complex and time-consuming processes.

To address these issues, MIT researchers have developed a new toxicity test that can precisely evaluate chemical effects on cell survival much faster than existing techniques. It could help academic scientists and pharmaceutical companies examine new drugs more quickly.

Traditional Approach

Colony formation assay (CFA) is the best available method for examining cell survival, in which cell colonies are grown in tissue culture dishes for 2 to 3 weeks. During this period, cells are usually exposed to radiation or chemical compounds. Then, one needs to count the number of colonies (which takes hours) to determine the effects of chemicals on cells.

Also, the counting process requires a lot of attention because a researcher has to constantly decide which one is a colony and which one is debris. Since this technique requires massive amounts of cell growth media (thus a large number of compounds have to be tested), a few scientists have stopped using CFA.

They have switched to other techniques — such as CellTiter-Glo and XTT — that are faster but not as sensitive and precise as the CFA. These tests inspect the mitochondrial function rather than measuring cell growth directly.

MicroColonyChip: The New Method

The MIT researchers wanted to formulate a method that could yield effective results in days (instead of weeks) without compromising with sensitivity and accuracy levels. They built MicroColonyChip that contains tiny wells on a plate.

Both processed and unprocessed cells are placed into tiny wells, where they start to produce small colonies in grids. After a few days, scientists can image the fluorescently labeled DNA of cells, using a conventional microscope.

Fluorescently labeled DNA | Courtesy of researchers

They don’t need to manually count the amount of fluorescent DNA, as researchers have developed a software program that evaluates the cell growth in each well. Furthermore, the toxicity of chemical compound(s) can be determined by comparing the growth of processed and unprocessed cells.

Testing

The team tested their method against CFA and discovered that the outcomes were almost identical. They also compared it with other popular toxicity tests (CellTiter-Glo and XTT) that are used by many drug companies.

CellTiter-Glo analyzes intracellular levels of adenosine triphosphate (molecules used to store and transport chemical energy within cells), whereas XTT examines the ability of cells to break down tetrazolium, an important step in cellular metabolism.

The results showed that MicroColonyChip is as sensitive as CellTiter-Glo and much more sensitive than XTT, thus it allows you to observe ultra-fine alterations in cell survival.

The team was able to analyze the effects of two toxic drugs used in chemotherapy and discovered that MicroColonyChip could precisely recreate the outcomes obtained using CFA. The next plan is to test this method for a variety of other drugs and cells.